tbuckley/cabot-search huggingface dataset:
Randomized phase 2 study of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy in pretreated patients with metastatic biliary tract cancer.
Authors: Alice Markussen, Julia S. Johansen, Finn Ole Larsen, Susann Theile, Jane P. Hasselby, Gro Linno Willemoe, Torben Lorentzen, Kasper Madsen, Eva E. Wilken, Poul F. Geertsen, Claus Behrens, Inge Marie Svane, Dorte Nielsen, Inna Markovna Chen
Journal: Journal of Clinical Oncology (2023)

545 Background: The treatment options for patients with biliary tract cancer (BTC) are limited. The aim of this study was to evaluate the clinical benefit of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with BTC. Methods: In this phase 2 study with a Simon’s 2-stage optimal design, patients with BTC refractory to at least one line of prior chemotherapy were randomized 1:1 to receive SBRT of 15 Gy combined with nivolumab or nivolumab/ipilimumab stratified by performance status. Signed informed consent was obtained from all patients. The primary endpoint was clinical benefit rate (CBR) defined as the proportion of patients with stable disease, partial response (PR), or complete response according to RECIST 1.1. Decision on expansion independently for both arms was pending on CBR from the first stage. Secondary endpoints included overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Between September 2018 and January 2022, 61 patients (19 SBRT/nivolumab and 42 SBRT/nivolumab/ipilimumab) received at least one treatment. Forty-eight patients (79%) had cholangiocarcinoma (intrahepatic 41, perihilar 2, distal 4, unspecified 1) and 13 patients (21%) had gallbladder cancer. No responses were observed in SBRT/nivolumab arm and this cohort was closed for inclusion after first stage based on CBR of 11% (95% confidence interval (CI) 1-33). SBRT/nivolumab/ipilimumab resulted in CBR of 31% (95% CI 18-47) and an overall response rate of 11.9% (95% CI 4.0-25.6). Of the five patients that achieved a PR, the median duration of response was 4.4 months (95% CI 0.0-9.2). A median PFS of 1.7 months (95% CI 1.6-1.7) and 1.7 months (95% CI 1.6-1.8), and a median OS of 4.7 months (95% CI 3.2-6.2) and 5.0 months (95% CI 2.1-7.9) were observed for patients receiving SBRT/nivolumab and SBRT/nivolumab/ipilimumab, respectively. Treatment-related adverse events grade 3 or higher occurred in 3 (16%) patients in the SBRT/nivolumab arm and 13 (31%) patients in the SBRT/nivolumab/ipilimumab arm. One patient died due to hepatitis in the combination arm. Conclusions: The combination of SBRT/nivolumab/ipilimumab demonstrated anti-tumor activity and acceptable toxicities in patients with advanced BTC. Further studies are warranted. Clinical trial information: NCT02866383 .
TST001 (a high affinity humanized anti-claudin18.2 monoclonal antibody) in combination with nivolumab plus capecitabine and oxaliplatin as first-line or with nivolumab as late-line treatment in locally advanced and metastatic gastric/gastroesophageal junction (G/GEJ) cancer: Design of cohorts from a phase I/IIa study (TST001-1002).
Authors: Weijian Guo, Caroline Germa, Chuan Qi, Chunhua Qian, Jenny Yao, Jianming Wang, Lijuan Zhang, Xueming Qian, Zhenzhong Xia
Journal: Journal of Clinical Oncology (2023)

TPS476 Background: TST001 (osemitamab) is a high affinity recombinant humanized ADCC enhanced antibody that can specifically bind to the extracellular structure of claudin 18.2 protein and eliminate cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Pre-clinical studies have shown that TST001 has potent single agent anti-tumor activity and synergistic effect when used in combination with immune checkpoint inhibitors in claudin 18.2 positive tumors. In the ongoing phase I/IIa clinical trial (NCT04495296), TST001 alone or in combination with capecitabine and oxaliplatin (CAPOX) in the treatment of G/GEJ adenocarcinoma has revealed encouraging preliminary efficacy (IGCC 2022, ESMO 2022). The combination of TST001 with nivolumab (in 2 nd /3 rd line treatment) or nivolumab + standard of care chemotherapy (in 1 st line) are being explored in the same study. Methods: Each cohort includes a dose escalation phase in CLDN18.2 non-selected patients and a dose expansion phase in CLDN18.2 positive patients, aiming to identify the recommended Phase 2 dose and evaluate the safety, tolerability and preliminary efficacy of TST001 in combination with nivolumab plus CAPOX or nivolumab in patients with G/GEJ adenocarcinoma. First line, treatment naïve patients with HER2 negative or unknown, locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with CAPOX plus nivolumab until disease progression or unacceptable toxicity, with oxaliplatin for a maximum of 8 cycles and capecitabine per investigator’s discretion after that; 2 nd or 3 rd line patients with locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with nivolumab. AEs will be categorized by CTCAE v5.0. Efficacy will be evaluated every 6 weeks per RECIST1.1. These two cohorts will be initiated in September 2022 from about 40 sites in China. Combinations with nivolumab are being explored in the US study too (NCT04396821). Clinical trial information: NCT04495296 .
Combined transarterial chemoembolization and external beam radiotherapy for identifying surgical candidates for hepatocellular carcinoma with macroscopic vascular invasion: A propensity score-weighted analysis.
Authors: Sang Min Yoon, Sumin Lee, Jinhong Jung, Jonggi Choi, Ju Hyun Shim, Gi-Won Song, Jin-hong Park
Journal: Journal of Clinical Oncology (2023)

562 Background: To evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Methods: We retrospectively reviewed the patients treated with combined TACE and RT as a first-line treatment for HCC with MVI between 2010 and 2015. Some patients with objective responses underwent hepatic resection or liver transplantation. Surgical resectability was determined by the hepatobiliary and transplant surgeons of the multidisciplinary team for liver cancer. To investigate the role of surgery, patients with objective responses who did not undergo surgery were selected as a control group. The survival outcomes between the patients who received surgery and those who did not were compared using a propensity score-based stabilized inverse probability of treatment weighting method to minimize selection bias. Time-dependent survival analysis by surgery was performed. Results: Of the 170 patients with objective responses after combined TACE and RT, surgery was performed for 41 patients, including 8 liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumor and unilateral vascular involvement. After adjustment, the overall survival rates at 3 years were 61.0% and 28.6% in surgery and non-surgery groups, respectively. The most important prognostic factor for overall survival was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17–0.46; p-value &lt; 0.001). Complete response after TACE and RT was also a significant prognostic indicator for overall survival (adjusted HR, 0.41; 95% CI, 0.27–0.61; p-value &lt; 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery for postoperative bleeding or graft failure. Conclusions: Hepatic resection was significantly associated with improved overall survival in patients with objective responses after combined TACE and RT for HCC with MVI.
Patient perspectives on colorectal cancer care delivery during the COVID-19 pandemic: A qualitative interview study.
Authors: Rozanne Wilson, Maria Cecilia Vieira, Meaghan Roach, Nadya Prood, Anjali Belani, Laura Mesana, Suepattra Grace May
Journal: Journal of Clinical Oncology (2023)

33 Background: The COVID-19 pandemic generated unprecedented interruptions and impacts on healthcare services across the US, including cancer care delivery. Patient perspectives on navigating colorectal cancer (CRC) care throughout the pandemic have not been well documented. This study explored patient experiences and perspectives around CRC care delivery throughout the pandemic by examining the impacts of COVID-19 on planned treatment, healthcare access, and quality of care. Methods: Patients diagnosed with CRC prior to January 2020 and who received treatment for CRC during 2019 participated in this qualitative study. Semi-structured interviews explored treatment experiences before and during the pandemic and were conducted between December 2021 and March 2022. Thematic analysis was used to identify key themes. Results: Twenty-four patients with CRC (mean age 45.4 years [SD=9.7]; 75% female; 62.5% current stage IV) completed an interview. Participants reported diminished mental health as the most salient impact of the pandemic related to their CRC care. Participants expressed how difficult, isolating, and lonely they felt navigating cancer treatment, particularly as a result of visitor restriction policies that did not allow their support person (e.g., spouse) to be present during visits or stays. Increased anxiety, fear, and worry over how the pandemic may affect their planned cancer care, including fear of contracting the virus themselves, were major concerns. Other impacts experienced included barriers to physically accessing care facilities (e.g., reduced appointment availability, staffing shortages), delays to patients’ planned treatment (e.g., canceled surgery), and increased access to and use of telehealth, which was perceived as being more convenient and safer than in-person visits. Participant perspectives on the quality of care they received throughout the pandemic were based on frequency and personalization of patient-provider communication, ability to access their usual care and support services (e.g., care navigators, support groups), and provider attention to their mental health. To improve the quality of cancer care in a pandemic setting, participants recommended personalized and frequent communications from the oncology care team, holistic care that includes mental health support, and streamlined insurance preauthorization processes. Conclusions: While the long-term impacts of COVID-19 on CRC care delivery have yet to be fully understood, this study highlights the key challenges patients experienced while receiving CRC care during the pandemic. Recognizing the strain of the pandemic on patients’ mental health and well-being will help to ensure patient-provider communication and support services consider the short and long-term effects of the pandemic for cancer patients as well as help contribute to improved treatment-related outcomes.
The impact of viral etiology in yttrium-90–treated hepatocellular carcinoma.
Authors: Itamar Marie Naveh-Benjamin, Ruyun Jin, Kara D Romano, Tri Minh Le, Paul Raymond Kunk, Matthew Reilley, Paul Read, Einsley-Marie Janowski
Journal: Journal of Clinical Oncology (2023)

608 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is derived from a background of chronic inflammation from both viral and environmental factors. Recent data indicates that immune therapy efficacy is improved in virally mediated HCC. We sought to investigate what impact HCC etiology has on outcomes in patients treated with yttrium-90 (Y90). Methods: We conducted a retrospective review of patients with HCC treated at our institution with Y90 radiotherapy from 2005-2021. Clinical and treatment characteristics were recorded, including: age, stage, HCC etiology, performance status, Child Pugh class, liver mass/volume treated, dose, prior therapy, imaging characteristics and basic labs. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for local control (LC) and overall survival (OS) following Y90. Results: 67 patients and 196 distinct tumors treated with Y90 were identified. Median prescription dose was 110 Gy (range 44-157). Patients were stage I-IVB with the most frequent stages being II, IIIb and IIIa (34%, 21% and 19% patients, respectively). 49 patients (73%) were Child-Pugh A and 18 (27%) were Child-Pugh B. 5 patients only had hepatitis B (7%), 26 patients only had hepatitis C (39%), and 6 patients had both hepatitis B and C (9%). Median OS among all patients was 7.6 (95% CI 5.6-11.5) months following Y90. The LC rate of all treated lesions was 42% and 24% at 6 and 12 months, respectively. On UVA analysis, improved LC was associated with younger age ( p=0.019), smaller liver mass ( p=0.039), and Hepatitis B etiology ( p=0.018). On Cox regression survival analysis, worsened OS was associated with lower ECOG status ( p=0.024), advanced stage ( p=0.023), lower albumin ( p=0.001), higher AFP ( p&lt;0.001), and portal vein invasion/thrombosis ( p=0.006, p=0.010). On MVA, lower albumin, higher AFP, advance stage and prior sorafenib were significantly related to worsened OS. If hepatitis B or C was forced into the MVA, the hazard ratio was 0.6 (95% CI 0.3-1.04) with p=0.068. Conclusions: Our results indicate that viral etiology impacts LC in our patients. Larger studies are necessary to confirm these results and to determine whether viral etiology impacts OS.
Nab-paclitaxel combined with oxaliplatin and S-1 as conversion therapy for advanced gastric adenocarcinoma.
Authors: Ke Ji, Zhaode Bu, Heli Yang, Zhenning Wang, Funan Liu, Pin Liang, Yan Dong, Jie Zhang, Qun Zhao, Yang Liu, Jiafu Ji
Journal: Journal of Clinical Oncology (2023)

343 Background: Conversion therapy can improve the survival of patients with locally advanced unresectable or potentially resectable metastatic gastric adenocarcinoma. This study was conducted to evaluate the efficacy and safety of nab-paclitaxel combined with oxaliplatin and S-1 as a conversion therapy in gastric cancer. Methods: This was a single-arm, multicenter, open-label trial of patients with locally advanced unresectable or potentially resectable metastatic gastric adenocarcinoma. Eligible patients were administered nab-paclitaxel (150 mg/m 2 , day 1), oxaliplatin (85 mg/m 2 , day 1), and S-1 (80–120 mg/day, days 1–14) every 21 days for two or four cycles. Radiographic assessments were performed after two cycles of treatment. Subsequent treatment or surgery was decided by the investigator according to assessment results and patient's condition. The primary endpoint was R0 resection rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: From January 2020 to September 2022, 62 patients (49 males/13 females) with a median age of 58.9 years (range: 36–73) were enrolled in this study. Sixteen (25.8%) of the 62 patients had distant metastasis. The overall response rate and disease control rate of 54 patients who underwent at least one assessment were 61.1% (33/54, 95% CI: 46.9–74.1%) and 94.4% (51/54, 95% CI: 84.6–98.8%), respectively. Of the 39 patients who underwent surgery, 33 (84.6%, 95% CI: 69.5–94.1%) patients had an R0 resection, two had an R1 resection, and four had exploratory laparotomies. The pathological complete response rate was 15.4% (6/39, 95% CI: 6.4–31.2%). After a median follow-up time of 8.4 months, the 1-year PFS rate was 68.6% (95% CI: 53.4–83.8%), whereas the median PFS and OS were not reached. Seven patients died because of disease progression (5 patients who did not undergo surgery), myocardial infarction (1 patient), and electrolyte disturbance (1 patient). Treatment-related adverse events occurred in 82.3% (51/62) patients, although most events were grade 1–2. Common hematological toxicities were leukopenia (61.3%), neutropenia (54.8%), anemia (41.9%), and thrombocytopenia (30.6%). Common non-hematological treatment-related adverse events were nausea (53.2%), fatigue (43.5%), hepatic function abnormal (33.9%), neurotoxicity (29.0%), and diarrhea (24.2%). Conclusions: Nab-paclitaxel combined with oxaliplatin and S-1 showed promising efficacy and acceptable toxicity in patients with locally advanced unresectable or potentially resectable metastatic gastric cancer. Clinical trial information: NCT04047953 .
Defining equitable genomic testing uptake in gastrointestinal oncology: Ensuring capture of demographic data.
Authors: Ellana K Haakenstad, Lauren K. Brais, Arrien Bertram, Andrea Kruse, Alissa Gentile, Rachel A. Freedman, Neal Ian Lindeman, Olga N. Kozyreva, Pedro Sanz-Altamira, Christopher S. Lathan, Michael J. Hassett, Ethan Cerami, Annette S. Kim, Danielle Manning, Jonathan Nowak, Marios Giannakis, Robert Coleman Lindsley, William C. Hahn, Bruce E. Johnson, Nadine Jackson McCleary
Journal: Journal of Clinical Oncology (2023)

794 Background: Tumor genomic testing (GT) has increased diagnostic accuracy and treatment options for patients (pts) with cancer. Dana-Farber Cancer Institute (DFCI) has made GT accessible as an institute-supported research effort for &gt;10 yrs. We estimate 50% standard therapies and 15-35% clinical trials in Gastrointestinal Cancer Clinic (GCC) require GT to determine eligibility. Pts in GCC with certain cancers are eligible for GT as a clinical test – these include metastatic/locally advanced colorectal, gastric, pancreatic, or biliary cancers. Clinical testing requires CLIA lab certification and insurance reimbursement; research does not. Herein we ID gaps in our GT database. Methods: We reviewed data on GT uptake in GCC between 4/2015 - 6/2022. 20,096 pts were captured by the GT tracking system. Data included: testing ordered and completed (proportion, type, time to receiving tissue for testing [TR], time to testing completion [TC]). Demographic data is not captured in the tracking system; matching unique patient identifiers with electronic health record is pending. Results: Most pts received GT (57.6%); 12% were not eligible; 30.4% declined consent. Most testing was completed (67.6%), but 21.3% of tests failed (45.5% of these from insufficient tissue). Research testing (71%) comprised most tests, but clinical tests were completed faster (median 34 days research vs 20 days clinical). Ampullary (91%), anal (90%), colon (90%) had highest completion rates; pancreatic (59%), hepatocellular carcinoma (56%) had lowest (from insufficient viable tumor in submitted specimens). Conclusions: GCC has a robust recruitment program that has yielded high GT uptake. Given the frequency that GT is used for treatment and trials, building a demographically representative dataset is crucial, especially for pts with largest burden of morbidity and mortality from cancer. We ID'd data gaps in the GT tracking system, which lacks demographics and reason for not testing. Demographic data is available in the electronic health record but does not speak with the GT tracking system so this analysis is not routinely done. Ability to visualize this data is important to ensure equitable GT uptake. Future efforts will focus on improving rates of consent in genomics databases and cancer clinical trials. Genomic testing at Dana-Farber Cancer Institute Gastrointestinal Cancer Center, 4/2015 – 6/2022.[Table: see text]
NRG GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US).
Authors: Christopher Hanyoung Lieu, Yan Lin, Scott Kopetz, Samuel A. Jacobs, Peter C. Lucas, Ibrahim Halil Sahin, Dustin A. Deming, Philip Agop Philip, Theodore S. Hong, Yesenia Rojas-Khalil, Jonathan M. Loree, Norman Wolmark, Greg Yothers, Thomas J. George, Arvind Dasari
Journal: Journal of Clinical Oncology (2023)

TPS260 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage III A, B (all pts) and stage II, IIIC (ctDNA+ only) CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera™, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 mos per established guidelines vs . serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs . more intensive AC with addition of irinotecan (I) for 6 mos. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs . delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June, 2022. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .